Translocation of a Gut Pathobiont Drives Autoimmunity in Mice and Humans

Science. 2018 Mar 9;359(6380):1156-1161. doi: 10.1126/science.aar7201.

Abstract

Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.

Trial registration: ClinicalTrials.gov NCT02394964.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Autoantibodies / immunology
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / microbiology*
  • Autoimmunity / genetics*
  • Autoimmunity / immunology
  • Bacterial Translocation*
  • Bacterial Vaccines / immunology
  • DNA, Bacterial / analysis
  • Enterococcus / drug effects
  • Enterococcus / immunology
  • Enterococcus / physiology*
  • Gastrointestinal Microbiome / physiology*
  • Genetic Predisposition to Disease*
  • Hepatocytes / microbiology
  • Humans
  • Liver / microbiology
  • Mice
  • T-Lymphocytes / immunology

Substances

  • Anti-Bacterial Agents
  • Autoantibodies
  • Bacterial Vaccines
  • DNA, Bacterial

Associated data

  • ClinicalTrials.gov/NCT02394964